Sym004 vs Standard of Care in Subjects With Metastatic Colorectal Cancer

Symphogen

Status and phase: Completed; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Sym004 (9/6 mg/kg); Drug: Fluorouracil (5-FU); Drug: Sym004 (12 mg/kg); Other: Best Supportive Care (BSC); Drug: Capecitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02083653

Sym004-05

EMR200637-002 (Other Identifier)

2013-003829-29 (EudraCT Number)

Details and patient eligibility

About

This is a Phase 2, open-label, randomized, 3-arm trial investigating the efficacy of two Sym004 doses (Arm A and Arm B) compared with a control group (Arm C) in subjects with metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs).

Full description

This trial assesses the efficacy of two different weekly dosing regimens of Sym004 (Arm A: 12 mg/kg/week versus Arm B: 9 mg/kg loading dose followed by 6 mg/kg/week) compared with investigator's choice in terms of overall survival time in subjects with mCRC. Subjects assigned to Arm C will receive best supportive care (BSC), Fluorouracil (5-FU), or Capecitabine, per local standard of care.

Subjects will receive treatment until unacceptable toxicity, disease progression, withdrawal of consent, or until the subject meets any of the criteria for treatment discontinuation or trial discontinuation. Therefore, the duration of treatment will differ among individuals and cannot be fixed in advance.

Enrollment: 254 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent obtained before undergoing any study-related activities
• Male or female, at least 18 years of age
• Subjects with histologically or cytologically confirmed mCRC, Kirsten rat sarcoma wild-type (KRAS WT) at initial diagnosis
• Failure of or intolerance to 5-FU, Oxaliplatin, and Irinotecan
• Acquired resistance to marketed anti-EGFR mAbs as defined in the protocol
• Measurable disease defined as one or more target lesions according to RECIST
• Life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
• Other protocol defined inclusion criteria could apply

Exclusion criteria

• Pretreatment with regorafenib.
• Subjects who in the opinion of the subject and investigator would benefit more from regorafenib treatment (except where regorafenib is not reimbursed in the country)
• Skin rash Common Terminology Criteria for AEs (CTCAE) Grade greater than 1 from previous anti-EGFR therapy at time of randomization
• Magnesium less than 0.9 milligram per deciliter (mg/dL)
• Known hypersensitivity to any of the treatment ingredients. Known previous Grade 3-4 infusion related reactions with anti-EGFR mABs
• Other protocol defined exclusion criteria could apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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254 participants in 3 patient groups

Arm A: Sym004 (12 mg/kg)

Experimental group

Description:

Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Treatment:

Drug: Sym004 (12 mg/kg)

Arm B: Sym004 (9/6 mg/kg)

Experimental group

Description:

Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal.

Treatment:

Drug: Sym004 (9/6 mg/kg)

Arm C: Investigator's Choice

Active Comparator group

Description:

Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Treatment:

Drug: Capecitabine

Other: Best Supportive Care (BSC)

Drug: Fluorouracil (5-FU)